Transplantation of islets of Langerhans for the clinical treatment of Type I diabetes has had a resurgence of interest due to results obtained using the "Edmonton protocol". However, at this time, procurement of donor pancreases for islet isolation and transplantation is in its infancy. Most pancreases at more remote donor sites are not procured due to justified concerns about post-mortem ischemia during transport to the islet isolation and transplant center. Perfusion/preservation technology has been shown to have a major impact in circumventing ischemic injury in kidney transplantation. This proposal seeks to apply this approach to the preservation and procurement of viable islets for transplantation. The primary objective of this proposal is to use state-of-the-art perfusion technology and new preservation solutions to test the hypothesis that machine perfusion can improve the yield and viability of islets prepared from ischemic pancreases. To this end, a prototype pancreas transporter (PTR) was designed and constructed in the Phase I study. The feasibility of 24h perfusion preservation at 2-7[unreadable]C was demonstrated using a porcine model that exceeds the 16h documented to be the present clinical limits of safe, static cold storage of donor pancreatic. Islet yield and function was demonstrated to be equivalent to that obtained from fresh control pancreases. The safety and efficacy of this new technology will be further investigated during this Phase II study with three specific aims. The first step will be to implement design modifications to the PTR ensuing from the Phase I feasibility study. The second step will entail a comparison of the yield and function indices for islets isolated from pancreata perfused for 24h on the PTR with indices obtained from control, 24h conventionally stored pancreata. Then the interaction between cold perfusion time (24 and 48h) and warm ischemia time (up to 60 min) on porcine islet isolation parameters will be evaluated for the definition of the potential clinical scope and technology limits. Finally, human pancreases that are unsuitable for transplantation will be employed for pre-clinical validation of this technology. It is anticipated that the availability of a pancreas transporter and pancreas perfusion protocols will permit utilization of most, if not all, pancreases suitable for transplantation in the U.S. Furthermore, the PTR may permit islet isolation banking for long-term storage. Banking would allow time for better HLA matching of donors to recipients, off-the-shelf availability, and enable quality assurance/control procedures to be conducted prior to transplantation. This research program is supported by collaboration with three major clinical centers interested in validation of this perfusion technology for their future use. [unreadable] [unreadable]